NM_000051.4(ATM):c.6136del (p.Ala2045_Leu2046insTer) AND Ataxia-telangiectasia syndrome

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Feb 25, 2022
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV003084892.10

Allele description [Variation Report for NM_000051.4(ATM):c.6136del (p.Ala2045_Leu2046insTer)]

NM_000051.4(ATM):c.6136del (p.Ala2045_Leu2046insTer)

Genes:

ATM:ATM serine/threonine kinase [Gene - OMIM - HGNC]
C11orf65:chromosome 11 open reading frame 65 [Gene - HGNC]

Variant type:

Deletion

Cytogenetic location:

11q22.3

Genomic location:

Preferred name:

NM_000051.4(ATM):c.6136del (p.Ala2045_Leu2046insTer)

HGVS:

NC_000011.10:g.108316051del
NG_009830.1:g.98220del
NG_054724.1:g.158784del
NM_000051.4:c.6136delMANE SELECT
NM_001330368.2:c.641-6978del
NM_001351110.2:c.*39-6978del
NM_001351834.2:c.6136del
NP_000042.3:p.Ala2045_Leu2046insTer
NP_000042.3:p.Leu2046Terfs
NP_001338763.1:p.Ala2045_Leu2046insTer
LRG_135t1:c.6136del
LRG_135:g.98220del
LRG_135p1:p.Leu2046Terfs
NC_000011.9:g.108186776del
NC_000011.9:g.108186778del
NM_000051.3:c.6136delC

Molecular consequence:

NM_001330368.2:c.641-6978del - intron variant - [Sequence Ontology: SO:0001627]
NM_001351110.2:c.*39-6978del - intron variant - [Sequence Ontology: SO:0001627]
NM_000051.4:c.6136del - nonsense - [Sequence Ontology: SO:0001587]
NM_001351834.2:c.6136del - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:: Ataxia-telangiectasia syndrome (AT)
Synonyms:: Louis-Bar syndrome; Cerebello-oculocutaneous telangiectasia; Immunodeficiency with ataxia telangiectasia; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0008840; MedGen: C0004135; Orphanet: 100; OMIM: 208900

Recent activity

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RecName: Full=Methylthioribulose-1-phosphate dehydratase; Short=MTRu-1-P dehydra...
RecName: Full=Methylthioribulose-1-phosphate dehydratase; Short=MTRu-1-P dehydratase; AltName: Full=APAF1-interacting protein; Short=hAPIP
gi|74731866|sp|Q96GX9.1|MTNB_HUMAN

Protein
CD44 [Nothoprocta perdicaria]
CD44 [Nothoprocta perdicaria]
Gene ID:112943559

Gene
Hypercalcemia
Hypercalcemia
Abnormally high level of calcium in the blood.<br/>Year introduced: MILK-ALKALI SYNDROME was see under HYPERCALCEMIA 1978-1983, was see under CALCINOSIS 1975-1977

MeSH
Diagnostic Errors
Diagnostic Errors
Incorrect or incomplete diagnoses following clinical or technical diagnostic procedures.<br/>Year introduced: 1973(1970)

MeSH

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003484129	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Feb 25, 2022)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 30549301, 23807571, 25614872, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003484129

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Feb 25, 2022)

germline

clinical testing

PubMed (4)
[See all records that cite these PMIDs]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Genotype, extrapyramidal features, and severity of variant ataxia-telangiectasia.

Schon K, van Os NJH, Oscroft N, Baxendale H, Scoffings D, Ray J, Suri M, Whitehouse WP, Mehta PR, Everett N, Bottolo L, van de Warrenburg BP, Byrd PJ, Weemaes C, Willemsen MA, Tischkowitz M, Taylor AM, Hensiek AE.

Ann Neurol. 2019 Feb;85(2):170-180. doi: 10.1002/ana.25394.

PubMed [citation]

PMID:: 30549301
PMCID:: PMC6590299

Twelve novel Atm mutations identified in Chinese ataxia telangiectasia patients.

Huang Y, Yang L, Wang J, Yang F, Xiao Y, Xia R, Yuan X, Yan M.

Neuromolecular Med. 2013 Sep;15(3):536-40. doi: 10.1007/s12017-013-8240-3. Epub 2013 Jun 27. Erratum in: Neuromolecular Med. 2014 Mar;16(1):216.

PubMed [citation]

PMID:: 23807571
PMCID:: PMC3732755

See all PubMed Citations (4)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV003484129.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

Description

For these reasons, this variant has been classified as Pathogenic. This premature translational stop signal has been observed in individual(s) with clinical features of ataxia-telangiectasia (PMID: 30549301). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Leu2046*) in the ATM gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in ATM are known to be pathogenic (PMID: 23807571, 25614872).

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Oct 26, 2024

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